Assessing the Feasibility of Linkage Disequilibrium Methods for Mapping Complex Traits: An Initial Screen for Bipolar Disorder Loci on Chromosome 18
Linkage disequilibrium (LD) analysis has been promoted as a method of mapping disease genes, particularly in isolated populations, but has not yet been used for genome-screening studies of complex disorders. We present results of a study to investigate the feasibility of LD methods for genome screen...
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| Veröffentlicht in: | American journal of human genetics 1999-06, Vol.64 (6), p.1670-1678 |
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| creator | Escamilla, Michael A. McInnes, L. Alison Spesny, Mitzi Reus, Victor I. Service, Susan K. Shimayoshi, Norito Tyler, David J. Silva, Sandra Molina, Julio Gallegos, Alvaro Meza, Luis Cruz, Maria L Batki, Steven Vinogradov, Sophia Neylan, Thomas Nguyen, Jasmine B. Fournier, Eduardo Araya, Carmen Barondes, Samuel H. Leon, Pedro Sandkuijl, Lodewijk A. Freimer, Nelson B. |
| description | Linkage disequilibrium (LD) analysis has been promoted as a method of mapping disease genes, particularly in isolated populations, but has not yet been used for genome-screening studies of complex disorders. We present results of a study to investigate the feasibility of LD methods for genome screening using a sample of individuals affected with severe bipolar mood disorder (BP-I), from an isolated population of the Costa Rican central valley. Forty-eight patients with BP-I were genotyped for markers spaced at ∼6-cM intervals across chromosome 18. Chromosome 18 was chosen because a previous genome-screening linkage study of two Costa Rican families had suggested a BP-I locus on this chromosome. Results of the current study suggest that LD methods will be useful for mapping BP-I in a larger sample. The results also support previously reported possible localizations (obtained from a separate collection of patients) of BP-I–susceptibility genes at two distinct sites on this chromosome. Current limitations of LD screening for identifying loci for complex traits are discussed, and recommendations are made for future research with these methods. |
| doi_str_mv | 10.1086/302400 |
| format | Article |
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Alison ; Spesny, Mitzi ; Reus, Victor I. ; Service, Susan K. ; Shimayoshi, Norito ; Tyler, David J. ; Silva, Sandra ; Molina, Julio ; Gallegos, Alvaro ; Meza, Luis ; Cruz, Maria L ; Batki, Steven ; Vinogradov, Sophia ; Neylan, Thomas ; Nguyen, Jasmine B. ; Fournier, Eduardo ; Araya, Carmen ; Barondes, Samuel H. ; Leon, Pedro ; Sandkuijl, Lodewijk A. ; Freimer, Nelson B.</creator><creatorcontrib>Escamilla, Michael A. ; McInnes, L. Alison ; Spesny, Mitzi ; Reus, Victor I. ; Service, Susan K. ; Shimayoshi, Norito ; Tyler, David J. ; Silva, Sandra ; Molina, Julio ; Gallegos, Alvaro ; Meza, Luis ; Cruz, Maria L ; Batki, Steven ; Vinogradov, Sophia ; Neylan, Thomas ; Nguyen, Jasmine B. ; Fournier, Eduardo ; Araya, Carmen ; Barondes, Samuel H. ; Leon, Pedro ; Sandkuijl, Lodewijk A. ; Freimer, Nelson B.</creatorcontrib><description>Linkage disequilibrium (LD) analysis has been promoted as a method of mapping disease genes, particularly in isolated populations, but has not yet been used for genome-screening studies of complex disorders. We present results of a study to investigate the feasibility of LD methods for genome screening using a sample of individuals affected with severe bipolar mood disorder (BP-I), from an isolated population of the Costa Rican central valley. Forty-eight patients with BP-I were genotyped for markers spaced at ∼6-cM intervals across chromosome 18. Chromosome 18 was chosen because a previous genome-screening linkage study of two Costa Rican families had suggested a BP-I locus on this chromosome. Results of the current study suggest that LD methods will be useful for mapping BP-I in a larger sample. The results also support previously reported possible localizations (obtained from a separate collection of patients) of BP-I–susceptibility genes at two distinct sites on this chromosome. Current limitations of LD screening for identifying loci for complex traits are discussed, and recommendations are made for future research with these methods.</description><identifier>ISSN: 0002-9297</identifier><identifier>EISSN: 1537-6605</identifier><identifier>DOI: 10.1086/302400</identifier><identifier>PMID: 10330354</identifier><identifier>CODEN: AJHGAG</identifier><language>eng</language><publisher>Chicago, IL: Elsevier Inc</publisher><subject>Adult and adolescent clinical studies ; Biological and medical sciences ; Bipolar disorder ; Bipolar Disorder - genetics ; Bipolar disorders ; Chromosome Mapping ; Chromosomes, Human, Pair 18 ; Costa Rica ; Genetics ; Genotype ; Humans ; Likelihood Functions ; Linkage Disequilibrium ; Medical genetics ; Medical sciences ; Mental and behavioral disorders ; Mood disorders ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. 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Alison</creatorcontrib><creatorcontrib>Spesny, Mitzi</creatorcontrib><creatorcontrib>Reus, Victor I.</creatorcontrib><creatorcontrib>Service, Susan K.</creatorcontrib><creatorcontrib>Shimayoshi, Norito</creatorcontrib><creatorcontrib>Tyler, David J.</creatorcontrib><creatorcontrib>Silva, Sandra</creatorcontrib><creatorcontrib>Molina, Julio</creatorcontrib><creatorcontrib>Gallegos, Alvaro</creatorcontrib><creatorcontrib>Meza, Luis</creatorcontrib><creatorcontrib>Cruz, Maria L</creatorcontrib><creatorcontrib>Batki, Steven</creatorcontrib><creatorcontrib>Vinogradov, Sophia</creatorcontrib><creatorcontrib>Neylan, Thomas</creatorcontrib><creatorcontrib>Nguyen, Jasmine B.</creatorcontrib><creatorcontrib>Fournier, Eduardo</creatorcontrib><creatorcontrib>Araya, Carmen</creatorcontrib><creatorcontrib>Barondes, Samuel H.</creatorcontrib><creatorcontrib>Leon, Pedro</creatorcontrib><creatorcontrib>Sandkuijl, Lodewijk A.</creatorcontrib><creatorcontrib>Freimer, Nelson B.</creatorcontrib><title>Assessing the Feasibility of Linkage Disequilibrium Methods for Mapping Complex Traits: An Initial Screen for Bipolar Disorder Loci on Chromosome 18</title><title>American journal of human genetics</title><addtitle>Am J Hum Genet</addtitle><description>Linkage disequilibrium (LD) analysis has been promoted as a method of mapping disease genes, particularly in isolated populations, but has not yet been used for genome-screening studies of complex disorders. We present results of a study to investigate the feasibility of LD methods for genome screening using a sample of individuals affected with severe bipolar mood disorder (BP-I), from an isolated population of the Costa Rican central valley. Forty-eight patients with BP-I were genotyped for markers spaced at ∼6-cM intervals across chromosome 18. Chromosome 18 was chosen because a previous genome-screening linkage study of two Costa Rican families had suggested a BP-I locus on this chromosome. Results of the current study suggest that LD methods will be useful for mapping BP-I in a larger sample. The results also support previously reported possible localizations (obtained from a separate collection of patients) of BP-I–susceptibility genes at two distinct sites on this chromosome. Current limitations of LD screening for identifying loci for complex traits are discussed, and recommendations are made for future research with these methods.</description><subject>Adult and adolescent clinical studies</subject><subject>Biological and medical sciences</subject><subject>Bipolar disorder</subject><subject>Bipolar Disorder - genetics</subject><subject>Bipolar disorders</subject><subject>Chromosome Mapping</subject><subject>Chromosomes, Human, Pair 18</subject><subject>Costa Rica</subject><subject>Genetics</subject><subject>Genotype</subject><subject>Humans</subject><subject>Likelihood Functions</subject><subject>Linkage Disequilibrium</subject><subject>Medical genetics</subject><subject>Medical sciences</subject><subject>Mental and behavioral disorders</subject><subject>Mood disorders</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. 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Alison ; Spesny, Mitzi ; Reus, Victor I. ; Service, Susan K. ; Shimayoshi, Norito ; Tyler, David J. ; Silva, Sandra ; Molina, Julio ; Gallegos, Alvaro ; Meza, Luis ; Cruz, Maria L ; Batki, Steven ; Vinogradov, Sophia ; Neylan, Thomas ; Nguyen, Jasmine B. ; Fournier, Eduardo ; Araya, Carmen ; Barondes, Samuel H. ; Leon, Pedro ; Sandkuijl, Lodewijk A. ; Freimer, Nelson B.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c432t-a22e3951b7d28f80a9a05155a7511e4525a662948450c158c4954f2414359a343</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>Adult and adolescent clinical studies</topic><topic>Biological and medical sciences</topic><topic>Bipolar disorder</topic><topic>Bipolar Disorder - genetics</topic><topic>Bipolar disorders</topic><topic>Chromosome Mapping</topic><topic>Chromosomes, Human, Pair 18</topic><topic>Costa Rica</topic><topic>Genetics</topic><topic>Genotype</topic><topic>Humans</topic><topic>Likelihood Functions</topic><topic>Linkage Disequilibrium</topic><topic>Medical genetics</topic><topic>Medical sciences</topic><topic>Mental and behavioral disorders</topic><topic>Mood disorders</topic><topic>Psychology. 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We present results of a study to investigate the feasibility of LD methods for genome screening using a sample of individuals affected with severe bipolar mood disorder (BP-I), from an isolated population of the Costa Rican central valley. Forty-eight patients with BP-I were genotyped for markers spaced at ∼6-cM intervals across chromosome 18. Chromosome 18 was chosen because a previous genome-screening linkage study of two Costa Rican families had suggested a BP-I locus on this chromosome. Results of the current study suggest that LD methods will be useful for mapping BP-I in a larger sample. The results also support previously reported possible localizations (obtained from a separate collection of patients) of BP-I–susceptibility genes at two distinct sites on this chromosome. 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| ispartof | American journal of human genetics, 1999-06, Vol.64 (6), p.1670-1678 |
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| source | MEDLINE; Cell Press Free Archives; ScienceDirect Journals (5 years ago - present); EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | Adult and adolescent clinical studies Biological and medical sciences Bipolar disorder Bipolar Disorder - genetics Bipolar disorders Chromosome Mapping Chromosomes, Human, Pair 18 Costa Rica Genetics Genotype Humans Likelihood Functions Linkage Disequilibrium Medical genetics Medical sciences Mental and behavioral disorders Mood disorders Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Quantitative Trait, Heritable |
| title | Assessing the Feasibility of Linkage Disequilibrium Methods for Mapping Complex Traits: An Initial Screen for Bipolar Disorder Loci on Chromosome 18 |
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